Search

Minimal invasive liver resections are a safe alternative to open surgery. Different scoring systems considering different risks factors have been developed to predict the risks associated with these procedures, especially challenging major liver resections (MLR). However, the impact of neoadjuvant chemotherapy (NAT) on the difficulty of minimally invasive MLRs remains poorly investigated. Patients who underwent laparoscopic and robotic MLRs for colorectal liver metastases (CRLM) performed across 57 centers between January 2005 to December 2021 were included in this analysis. Patients who did or did not receive NAT were matched based on 1:1 coarsened exact and 1:2 propensity-score matching. Pre- and post-matching comparisons were performed. In total, the data of 5189 patients were reviewed. Of these, 1411 procedures were performed for CRLM, and 1061 cases met the inclusion criteria. After excluding 27 cases with missing data on NAT, 1034 patients (NAT: n = 641; non-NAT: n = 393) were included. Before matching, baseline characteristics were vastly different. Before matching, the morbidity rate was significantly higher in the NAT-group (33.2% vs. 27.2%, p-value = 0.043). No significant differences were seen in perioperative outcomes after the coarsened exact matching. After the propensity-score matching, statistically significant higher blood loss (mean, 300 (SD 128–596) vs. 250 (SD 100–400) ml, p-value = 0.047) but shorter hospital stay (mean, 6 [ 4-8] vs. 6 [ 5-9] days, p-value = 0.043) were found in the NAT-group. The current study demonstrated that NAT had minimal impact on the difficulty and outcomes of minimally-invasive MLR for CRLM. Abbreviated abstract: The impact of neoadjuvant chemotherapy (NAT) on the difficulty of minimally invasive major liver resections (MLRs) remains poorly investigated. NAT had minimal impact on the difficulty and outcomes of minimally-invasive MLR for colorectal liver metastases. [ABSTRACT FROM AUTHOR]

Today, there is still debate on the impact of neoadjuvant chemotherapy (NeoChem) on liver regeneration (LivReg). The objectives of this study were to assess the impact of NeoChem and its characteristics (addition of bevacizumab, number of cycles and time from end of NeoChem) on post-hepatectomy LivReg. Studies reporting LivReg in patients submitted to liver resection were included. Pubmed, Scopus, Web of Science, Embase, and Cochrane databases were searched. Only studies comparing NeoChem vs no chemotherapy or comparing chemotherapy characteristics from 1990 to present were included. Two researchers individually screened the identified records registered in a predesigned database. Primary outcome was future liver remnant regeneration rate (FLR3). Bias of the studies was evaluated with the ROBINS-I tool, and quality of evidence with the GRADE system. Data was presented as mean difference or standard mean difference. Eight studies with a total of 681 patients were selected. Seven were retrospective and one prospective comparative cohort studies. In patients submitted to major hepatectomy, NeoChem did not have an impact on LivReg (MD 3.12, 95% CI -2,12–8.36, p 0,24). Adding bevacizumab to standard NeoChem was associated with better FLR3 (SMD 0.45, 95% CI 0.19–0.71, p 0.0006). The main drawback of this review is the retrospective nature of the available studies. NeoChem does not have a negative impact on postoperative LivReg in patients submitted to liver resection. Regimens with bevacizumab seem to be associated with better postoperative LivReg rates when compared to standard NeoChem. This is a systematic review and meta-analysis of the effect of neoadjuvant chemotherapy on post-hepatectomy liver regeneration. [ABSTRACT FROM AUTHOR]

The histological responses (HRs) after systemic chemotherapy should be used to determine the optimal management of patients with peritoneal and liver metastasis from colorectal cancer (cPM, cLM), in curative intent. We aimed to compare HRs of cPM and cLM in metastatic mice model after chemotherapy. Colon carcinoma CT26-luc cells were transplanted into syngeneic BALB/c mice by intraperitoneal (leading to cPM), intrasplenic (leading to cLM), or intraperitoneal + intrasplenic (leading to cPM cLM) injections and follow up using bioluminescence during 21 days. Bi-chemotherapeutic treatment (5-fluorouracil at D11, D17, and D20, and oxaliplatin at D13 and D19) was administered. The peritoneal cancer index (PCI) and HRs using Peritoneal Regression Grading Score (PRGS) and Tumor Regression Grade (TRG) classifications were analyzed at day 21. Unlike bioluminescence rate, PCI was reduced after chemotherapy in all treated groups with cPM comparatively to controls (33 ± 9.5 vs. 19.8 ± 5, p = 0.002 for cPM groups; 37.7 ± 3.6 vs. 25.2 ± 10.8, p = 0.0003 for the cPM + cLM groups). The complete or major HR rates were higher in all treated groups compared to the non-treated mice (cPM, 2.29 ± 0.55 vs. 3.56 ± 1.01; cLM, 2.43 ± 1.89 vs. 4.86 ± 0.378; cPM + cLM, 2.73 ± 1.03 and 2.2 ± 0.65 vs. 3.79 ± 0.75 and 4.36 ± 0.43). The complete or major HR rates after chemotherapy were similar across the metastatic sites in 60% for cPM + cLM group. The efficacy of chemotherapeutic treatment did not differ between the metastatic sites. Murine models are suitable in histological analyses to study tumor development and regression but clinical study will be performed to confirm these results. [ABSTRACT FROM AUTHOR]

Although numerous comparisons between conventional Two Stage Hepatectomy (TSH) and Associating Liver Partition and Portal Vein Ligation for staged hepatectomy (ALPPS) have been reported, the heterogeneity of malignancies previously compared represents an important source of selection bias. This systematic review and meta-analysis aimed to compare perioperative and oncological outcomes between TSH and ALPPS to treat patients with initially unresectable colorectal liver metastases (CRLM). Main electronic databases were searched using medical subject headings for CRLM surgically treated with TSH or ALPPS. Patients treated for primary or secondary liver malignancies other than CRLM were excluded. A total of 335 patients from 5 studies were included. Postoperative major complications were higher in the ALPPS group (relative risk [RR] 1.46, 95% confidence interval [CI] 1.04–2.06, I 2 = 0%), while no differences were observed in terms of perioperative mortality (RR 1.53, 95% CI 0.64–3.62, I 2 = 0%). ALPPS was associated with higher completion of hepatectomy rates (RR 1.32, 95% CI 1.09–1.61, I 2 = 85%), as well as R0 resection rates (RR 1.61, 95% CI 1.13–2.30, I 2 = 40%). Nevertheless, no significant differences were achieved between groups in terms of overall survival (OS) (RR 0.93, 95% CI 0.68–1.27, I 2 = 52%) and disease-free survival (DFS) (RR 1.08, 95% CI 0.47–2.49, I 2 = 54%), respectively. ALPPS and TSH to treat CRLM seem to have comparable operative risks in terms of mortality rates. No definitive conclusions regarding OS and DFS can be drawn from the results. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare healthcare related costs and survival in patients treated with microwave ablation (MWA) versus surgical resection for resectable colorectal liver metastases (CRLM), in patients from a quasi-randomised setting. The Swedish subset of data from a prospective multi-centre study investigating survival after percutaneous computer-assisted M icrowave A blation VE rsus R esection for R esectab l e C RLM (MAVERRIC study) was analysed. Patients with CRLM ≤ 3 cm amenable to ablation and resection were considered for study inclusion only on even calendar weeks, while treated with gold standard resection every other week, creating a quasi-randomised setting. Survival and costs (all inpatient hospital admissions, outpatient visits, oncological treatments and radiological imaging) in the 2 years following treatment were investigated. MWA (n = 52) and resection (n = 53) cohorts had similar baseline patient and tumour characteristics and health care consumption within 1 year prior to CRLM treatment. Treatment related morbidity and length of stay were significantly higher in the resected cohort. Overall health care related costs from decision of treatment and 2 years thereafter were lower in the MWA versus resection cohort (mean ± SD USD 80′964±59′182 versus 110′059±59′671, P < 0.01). Five-year overall survival was 50% versus 54% in MWA versus resection groups (P = 0.95). MWA is associated with decreased morbidity, time spent in medical facilities and healthcare related costs within 2 years of initial treatment with equal overall survival, highlighting its benefits for patient and health care systems. [ABSTRACT FROM AUTHOR]

The histological growth pattern (HGP) of colorectal liver metastases (CRLMs) reflects tumor biology and local infiltrating behavior. In patients undergoing surgery for CRLMs, we investigated whether HGP and surgical margin status interact when influencing prognosis. Clinicopathological data, margin status, and HGP were reviewed in patients who underwent resection of CRLMs. R1 margin was defined when cancer cells were present at any point along the margin. HGPs were scored according to international guidelines, identifying patients with desmoplastic (DHGP) or non-desmoplastic (non-DHGP) CRLMs. Among 299 patients, 16% had R1 resection and 81% had non-DHGP CRLMs. Non-DHGP was the only predictive factor for R1 resection (18.7% versus 7.4% in DHGP, p = 0.04). Poorer 5-year overall survival was observed in both R1 and non-DHGP groups in univariate analysis (27.6% in R1 versus 45.6% in R0, p = 0.026, and 37.2% in non-DHGP versus 59.2% in DHGP, p = 0.013), whereas non-DHGP but not R1 remained associated with worse prognosis in multivariate analysis. In patients with non-DHGP, R1 margin has no prognostic impact. In patients undergoing resection of CRLMs, the prognostic value of poor tumor biology, such as in patients with non-DHGP, exceeds that of surgical radicality. [ABSTRACT FROM AUTHOR]

Textbook outcome (TO) is a composite outcome measure covering the surgical care process in a single outcome measure. TO has an advantage over single outcome parameters with low event rates, which have less discriminating impact to detect differences between hospitals. This study aimed to assess factors associated with TO, and evaluate hospital and network variation after case-mix correction in TO rates for liver surgery. This was a population-based retrospective study of all patients who underwent liver resection for malignancy in the Netherlands in 2019 and 2020. TO was defined as absence of severe postoperative complications, mortality, prolonged length of hospital stay, and readmission, and obtaining adequate resection margins. Multivariable logistic regression was used for case-mix adjustment. 2376 patients were included. TO was accomplished in 1380 (80%) patients with colorectal liver metastases, in 192 (76%) patients with other liver metastases, in 183 (74%) patients with hepatocellular carcinoma and 86 (51%) patients with biliary cancers. Factors associated with lower TO rates for CRLM included ASA score ≥3 (aOR 0.70, CI 0.51–0.95 p = 0.02), extrahepatic disease (aOR 0.64, CI 0.44–0.95, p = 0.02), tumour size >55 mm on preoperative imaging (aOR 0.56, CI 0.34–0.94, p = 0.02), Charlson Comorbidity Index ≥2 (aOR 0.73, CI 0.54–0.98, p = 0.04), and major liver resection (aOR 0.50, CI 0.36–0.69, p < 0.001). After case-mix correction, no significant hospital or oncological network variation was observed. TO differs between indications for liver resection and can be used to assess between hospital and network differences. [ABSTRACT FROM AUTHOR]

Metastatic spread of colorectal cancer to the liver impacts prognosis. Advances in chemotherapy have resulted in increased resectability rates and thereby improved survival in patients with colorectal liver metastases (CRLM). However, criteria are needed to ensure that patients selected for hepatic resection benefit from the invasive therapy. The study aimed to construct a predictive model for overall survival (OS) in patients with CRLM, based on preoperatively available information. The retrospective cohort study reviewed all patients with CRLM discussed at multidisciplinary team conference at Karolinska University Hospital, Stockholm, Sweden, 2013–2018. Independent prognostic factors for OS were identified, based on which a score model was generated. The model was validated on patients treated for CRLM at Hôpital Universitaire Paul Brousse, Villejuif, France, 2007–2018. Calibration and discrimination methods were used for internal and external validation. The Swedish development cohort included 1013 patients, the French validation cohort 391 patients. Poor OS was significantly associated with age>60years (hazard ratio (HR) 3.57 (95%CI 2.18–9.94)), number of CRLM (HR 4.59 (2.83–12.20)), diameter of largest CRLM>5 cm (HR 2.59 (1.74–5.03)), right-sided primary tumour (HR 2.98 (2.00–5.80)), extrahepatic disease (HR 4.14 (2.38–15.87)) and non-resectability (HR 0.77 (0.66-0.90)). The C-statistic for prediction of OS was.74, in the development cohort and 0.69 in the validation cohort. The presented predictive score model can adequately predict OS for patients at the initial diagnosis of CRLM. The prognostic model could be of clinical value in the management of all patients with CRLM, by predicting individualized survival and thereby facilitating treatment recommendations. [ABSTRACT FROM AUTHOR]

Additional radiofrequency ablation (RFA) of liver-limited colorectal liver metastases (CRLM) improves overall (OS) and recurrence-free survival (RFS) over systemic therapy alone. We aimed to assess the potential and predictive factors of long-term survival and cure to optimize patient selection for RFA application. Retrospective review of a prospectively maintained single-center database of consecutive patients undergoing RFA for liver-limited CRLM after systemic therapy between 2002 and 2020. Clinicopathologic characteristics and KRAS/BRAF- genotype data (tested routinely since 2010) were correlated to RFS and OS. Cure was defined as ≥10-years RFS (long-term survival as ≥5-years OS) following RFA. For the entire cohort of 158 patients (median follow-up 13.6 years), co-occurrence of three factors, RECIST-defined response, number of ≤3 CRLM, and ≤3 cm maximum size determined a survival plateau that distinguished cured from non-cured patients (10-years RFS: 15.5% vs 0%, p < 0.0001). Among 59 patients (37.3%) being tested, 4(6.8%) were BRAF -mt, 15(25.4%) KRAS -mt, and 40(67.8%) KRAS/BRAF -wt. OS (median follow-up 8.3 years) was estimated to be higher with KRAS/BRAF -wt compared to a mutant KRAS or BRAF status (5-years OS: 22.8% vs 3.4%, p = 0.0018). This study indicates about 15% chance of cure following RFA of low-volume liver-limited CRLM after downsizing by systemic therapy and a negative effect of KRAS or BRAF mutation on long-term survival after CRLM ablation. These findings may improve clinical decision-making in patients potentially candidate to RFA of CRLM and encourage further investigations on molecular factors determining an oligometastatic state of CRLM curable with focal ablative therapy. [ABSTRACT FROM AUTHOR]

To use circulating tumor cells (CTC) from the first drainage vein (FDV) of the primary lesion and other clinically relevant parameters to construct a nomogram for predicting liver metastasis in colorectal cancer (CRC) patients, and to provide a theoretical basis for clinical diagnosis and treatment. Information from 343 CRC patients was collected and a database was established. Multivariate logistic analysis was used to identify independent factors for colorectal cancer liver metastasis(mCRC) and nomograms were constructed. Receiver operating characteristic curves(ROC), calibration plots, and decision curve analysis (DCA) were used to assess discrimination, agreement with actual risk, and the clinical utility of the prediction model, respectively. CTC levels in FDV were significantly higher in patients with liver metastasis than in those without liver metastasis. Logistic multivariate analysis showed that vascular invasion, T stage, carcinoembryonic antigen (CEA), CA19-9, and CTC could be used as predictors to construct nomograms. The nomograms showed good discriminatory ability in predicting mCRC, with area under the curve (AUC) values of 0.871 [95 % CI: 0.817–0.924) and 0.891 (95 % CI: 0.817–0.964) for the training and validation sets, respectively.] The calibration curves of both the training and validation sets showed that the model was effective in predicting the probability of mCRC. DCA was used to evaluate this predictive model and showed good net clinical benefit. We developed and validated a nomogram model based on the combination of CTC in the FDV with other clinical parameters to better predict the occurrence of mCRC. [ABSTRACT FROM AUTHOR]

Accurate prediction of patients at risk for early recurrence (ER) among patients with colorectal liver metastases (CRLM) following preoperative chemotherapy and hepatectomy remains limited. Patients with CRLM who received chemotherapy prior to undergoing curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. Multivariable Cox regression analysis was used to assess clinicopathological factors associated with ER, and an online calculator was developed and validated. Among 768 patients undergoing preoperative chemotherapy and curative-intent resection, 128 (16.7 %) patients had ER. Multivariable Cox analysis demonstrated that Eastern Cooperative Oncology Group Performance status ≥1 (HR 2.09, 95%CI 1.46–2.98), rectal cancer (HR 1.95, 95%CI 1.35–2.83), lymph node metastases (HR 2.39, 95%CI 1.60–3.56), mutated Kirsten rat sarcoma oncogene status (HR 1.95, 95%CI 1.25–3.02), increase in tumor burden score during chemotherapy (HR 1.51, 95%CI 1.03–2.24), and bilateral metastases (HR 1.94, 95%CI 1.35–2.79) were independent predictors of ER in the preoperative setting. In the postoperative model, in addition to the aforementioned factors, tumor regression grade was associated with higher hazards of ER (HR 1.91, 95%CI 1.32–2.75), while receipt of adjuvant chemotherapy was associated with lower likelihood of ER (HR 0.44, 95%CI 0.30–0.63). The discriminative accuracy of the preoperative (training: c-index: 0.77, 95%CI 0.72–0.81; internal validation: c-index: 0.79, 95%CI 0.75–0.82) and postoperative (training: c-index: 0.79, 95%CI 0.75–0.83; internal validation: c-index: 0.81, 95%CI 0.77–0.84) models was favorable (https://junkawashima.shinyapps.io/CRLMfollwingchemotherapy/). Patient-, tumor- and treatment-related characteristics in the preoperative and postoperative setting were utilized to develop an online, easy-to-use risk calculator for ER following resection of CRLM. [ABSTRACT FROM AUTHOR]

A nationwide multicenter study was performed to examine whether there is a correlation between decrease in tissue resistance and time to local tumor recurrence after irreversible electroporation (IRE) in patients with hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRCLM). All patients treated with IRE for liver tumors in Sweden from 2011 until 2018 were included. Patient characteristics and recurrence patterns were obtained from medical records and radiological imaging. All procedural data from the IRE hardware at the three hospitals performing IRE were retrieved. The resistance during each pulse and the change during each treatment were calculated. The electrode pair with the smallest decrease in tissue resistance was used and compared with the time to LTP. 149 patients with 206 tumors were treated. Exclusion due to missing and inaccurate data resulted in 124 patients with 170 tumors for the analyses. In a multivariable Cox regression model, a smaller decrease in tissue resistance and larger tumor size were associated with shorter time to local tumor recurrence for CRCLM, but not for HCC. There was an association between a decrease in tissue resistance and time to local tumor recurrence for CRCLM. The decrease in resistance, in combination with a rise in current, may be the parameters the interventionist should use during IRE to decide if the treatment is successful. • This is the first study to assess the importance of tissue resistance after delivery of irreversible electroporation and the risk of developing local tumor recurrence in patients with either hepatocellular carcinoma or liver metastases due to colorectal cancer. • This nationwide found an association between a decrease in tissue resistance and time to local tumor recurrence in colorectal cancer with liver metastases. • The decrease in resistance, instead of rise in current, could be the parameter the interventionist should use during IRE to decide if the treatment is successful. [ABSTRACT FROM AUTHOR]

Chemotherapy is widely used as an adjunct to surgery in the treatment of patients with resectable colorectal liver metastases. The aim of this study was to examine whether chemotherapy confers a survival benefit in patients with a solitary colorectal liver metastasis. All consecutive patients between 2009 and 2017 in Sweden who were resected for a solitary colorectal liver metastasis were included. Patients treated with chemotherapy were compared with patients who had surgery alone. Unmatched and propensity score matched analyses were performed to compare overall survival, morbidity and mortality. Of 1224 eligible patients, 641 (52.4%) patients had chemotherapy, and 583 (47.6%) had surgery alone. After propensity score matching, two balanced groups with 102 patients in each, were analyzed. There was no difference in readmission within 30-days (p = 0.250), or morbidity, defined as Clavien-Dindo 3a or greater, between the groups (p = 0.761). There were no mortalities within ninety days. Radical resection margins were achieved in 92 (n = 94) per cent in the chemotherapy group, and 77 (n = 78) per cent in the surgery alone group (p = 0.016). Median overall survival was 91 (95% CI 73–109) months in the chemotherapy group, and 78 (95% CI 37–119) months in the surgery-alone group (p = 0.652). This nationwide register-based study showed no difference in overall survival between patients treated with chemotherapy compared to surgery alone. Upfront surgery may be advisable in resectable solitary colorectal liver metastasis. [ABSTRACT FROM AUTHOR]

Contemporary management of colorectal cancer with synchronous liver metastases is complex. Although there is a large body of cohort data, there is no research exploring patient and clinician perspectives. This study explores the experiences and views of patients following treatment for colorectal cancer with synchronous liver metastases and the clinicians involved in their care. This is a qualitative study based on interviews with patients who had completed treatment for colorectal cancer with synchronous liver metastases and their treating clinicians. The interviews were recorded, transcribed and analysed using thematic analysis methods. Codes were developed both horizontally regarding each interview as a standalone hermeneutic unit and vertically by scanning across interviews for specific terms. Four overarching themes emerged: patients' experience of initial diagnosis, involvement in treatment, views on the order of staged resections and views about research. For patients, the first consultation is critically important. Patients generally perceived sufficient autonomy in decision-making. In treatment options there is a preference for synchronous surgery balanced by an understanding of the greater risk. Patients did not want liver-first surgery due to the perceived risk of continued seeding from an in situ primary tumour. Clinicians accepted limited evidence for decision making but felt that trials of treatment sequencing were not feasible. This first qualitative study explores patients' perceptions in colorectal cancer with synchronous liver metastases that are not possible to obtain from quantitative data. CoSMIC-Q demonstrates the importance of incorporating patients' views into treatment planning particularly where equipoise exists in surgical sequence. [ABSTRACT FROM AUTHOR]

Heterogenous response to neoadjuvant chemotherapy in patients with multiple colorectal liver metastases (CRLM) has been associated with an acquired resistance to systemic therapy. This study evaluated the occurrence of a heterogenous inter-metastatic tumour response with regards to the proportion of viable tumour cells, and its prognostic impact. A retrospective cohort study was conducted, including all patients with CRLM surgically treated at Karolinska University Hospital, Stockholm, Sweden, from 2013 to 2018. Factors associated with the proportion of viable tumour cells and inter-metastatic heterogeneity were analysed with regression and survival analyses. Out of 640 surgically treated patients, 405 patients (1357 CRLM), received neoadjuvant chemotherapy. Multiple CRLM were present in 314 patients (78%), out of whom 72 patients (23%) presented with a heterogenous tumour response. The median overall survival (OS) for patients with a heterogenous inter-metastatic tumour response was 36 months, compared to 57 months for patients with a homogenous inter-metastatic tumour response (p <.001). Poor OS in patients receiving preoperative chemotherapy was significantly associated with a heterogenous inter-metastatic tumour response (hazard ratio (HR) 1.68 (1.02–2.78)), right-sided primary tumour (HR 2.01 (1.29–3.43)) and CRLM diameter >5 cm (HR 1.83 (1.06–3.17)). Outcome in patients with a heterogenous inter-metastatic tumour response, illustrated by the proportion of viable tumour cells, is inferior to that of patients with a homogenous response. These results suggest that heterogeneity in treatment response is an important marker of aggressive disease and could be of clinical value for decisions on post-operative therapy. [ABSTRACT FROM AUTHOR]

Minimally invasive ablative treatments, such as radiofrequency ablation (RFA), are increasingly used in the curative treatment of patients with colorectal liver metastases (CRLM). Selection bias plays an important role in the evaluation of early and late results between RFA and surgery. The purpose of this study was to evaluate recurrences and oncological survival following these two treatment modalities using single pair propensity score matching. Between 2000 and 2018, patients curatively treated for CRLM were included in a multicentre database. Patients were excluded when receiving two-staged treatment, synchronous treatment with primary tumor or combination of modalities. Propensity score matching was used to minimize influence of known covariates, i.e., age, ASA, FONG CRS, location and T-stage of the primary tumor. Before matching, the RFA group contained 39 patients and the surgery group 982 patients, after matching both groups contained 36 patients. After matching, mean age was 69 years (53–86) for RFA and 68 (50–86) for surgery, with a mean tumor size of respectively 2.5 cm (0.8–6.5) and 3.4 cm (1–7.5). Both groups showed similar complication rate according to Clavien-Dindo (17vs.33%; p = 0.18), recurrence rate (58vs.64%; p = 0.09) without significant differences in 5-year DFS and OS (RFA compared to surgery respectively 25vs.37%; p = 0.09 and 42vs.53%; p = 0.09). After propensity score matching, RFA showed lower complications and similar oncological survival compared to surgical resection. In patients who are suboptimal candidates for surgery, RFA seems to be a good and safe alternative. [ABSTRACT FROM AUTHOR]

Data on the management of elderly patients with extensive colorectal liver metastases (CRLM) are scarce and conflicting. This study assesses differences in management and long-term oncological outcomes between older and younger patients with CRLM and a high Tumour Burden Score (TBS). International multicentre retrospective study on patients with CRLM and a category 3 TBS, submitted to liver resection. Patients were divided into two groups according to their age (younger and older than 75) and were compared using propensity score matching (PSM) analysis and multivariable regression models. Differences in management and oncological outcomes including recurrence-free survival (RFS) and overall survival (OS) were assessed. The study included 386 patients, median follow-up was 48 months. The unmatched comparison revealed a higher ASA score (p = 0.035), less synchronous CRLM (47% vs 68%, p = 0.003), a lower median number of lesions (1 vs 3, p = 0.004) and less perioperative chemotherapy (CTx) (66% vs 88%, p < 0.001) in the elderly group. Despite the absence of CTx being an independent predictor of decreased RFS and OS (HR 0.760, p = 0.044 and HR 0.719, p = 0.049, respectively), the elderly group still received less CTx (OR 0.317, p = 0.001) than the younger group. After PSM (n = 100 patients), the two groups were comparable, however, CTx administration was still significantly lower in the elderly group. Liver resection should be considered in patients aged 75 and older, even if they present with extensive liver disease. Despite CTx being associated with improved oncological outcomes, a large percentage of elderly patients with CRLM are undertreated. [ABSTRACT FROM AUTHOR]

In the last three decades, minimally invasive liver resection has been replacing conventional open approach in liver surgery. More recently, developments in neoadjuvant chemotherapy have led to increased multidisciplinary management of colorectal liver metastases with both medical and surgical treatment modalities. However, the impact of neoadjuvant chemotherapy on the surgical outcomes of minimally invasive liver resections remains poorly understood. A multicenter, international, database of 4998 minimally invasive minor hepatectomy for colorectal liver metastases was used to compare surgical outcomes in patients who received neoadjuvant chemotherapy with surgery alone. To correct for baseline imbalance, propensity score matching, coarsened exact matching and inverse probability treatment weighting were performed. 2546 patients met the inclusion criteria. After propensity score matching there were 759 patients in both groups and 383 patients in both groups after coarsened exact matching. Baseline characteristics were equal after both matching strategies. Neoadjuvant chemotherapy was not associated with statistically significant worse surgical outcomes of minimally invasive minor hepatectomy. Neoadjuvant chemotherapy had no statistically significant impact on short-term surgical outcomes after simple and complex minimally invasive minor hepatectomy for colorectal liver metastases. [ABSTRACT FROM AUTHOR]

Mutations in the BRAF gene (BRAFmut) are associated with an unfavorable prognosis in patients with metastatic colorectal cancer (CRC). The aim of this meta-analysis was to evaluate the prognosis of colorectal cancer (CRC) patients with liver metastases and the potential benefits of liver resection in patients with BRAFmut CRC. A systematic search of PubMed, Cochrane Central Controlled Trials, and Embase databases was conducted on May 31, 2023. The inclusion criteria were as follows:1) reporting of outcomes in patients with BRAFmut CRC who underwent surgery for liver metastases and/or comparison of outcomes between those who underwent and those who did not undergo resection; 2) reporting of survival information as hazard ratios (HR); and 3) publication in English. 34 studies were included. Median follow up was 48 months for prognostic BRAF status meta-analysis. BRAFmut status showed a significantly increased risk of mortality (hazard ratio [HR] = 2.56, 95% confidence interval [CI] 2.04–3.22; P < 0.01) and relapse (HR = 1.97, 95% CI 1.44–2.71; P < 0.01). Resection of liver metastases was associated with a survival benefit (median follow up 46 months). The HR for survival was 0.44 (95% confidence interval [CI] 0.33–0.59; P < 0.01) in favor of surgery. and Relevance: Our analysis indeed confirms that BRAF mutation is associated with poor survival outcomes after liver resection of CRC metastases. However, upon quantitatively assessing the survival benefit of surgical intervention in patients with BRAF-mutated CRC liver metastases, we identified a significant 56% reduction in the risk of death. [ABSTRACT FROM AUTHOR]

In 2013, the nationwide Dutch Hepato Biliary Audit (DHBA) was initiated. The aim of this study was to evaluate changes in indications for and outcomes of liver surgery in the last decade. This nationwide study included all patients who underwent liver surgery for four indications, including colorectal liver metastases (CRLM), hepatocellular carcinoma (HCC), and intrahepatic– and perihilar cholangiocarcinoma (iCCA – pCCA) between 2014 and 2022. Trends in postoperative outcomes were evaluated separately for each indication using multilevel multivariable logistic regression analyses. This study included 8057 procedures for CRLM, 838 for HCC, 290 for iCCA, and 300 for pCCA. Over time, these patients had higher risk profiles (more ASA-III patients and more comorbidities). Adjusted mortality decreased over time for CRLM, HCC and iCCA, respectively aOR 0.83, 95%CI 0.75–0.92 , P < 0.001; aOR 0.86, 95%CI 0.75–0.99, P = 0.045 ; aOR 0.40, 95%CI 0.20–0.73, P < 0.001. Failure to rescue (FTR) also decreased for these groups, respectively aOR 0.84, 95%CI 0.76–0.93, P = 0.001; aOR 0.81, 95%CI 0.68–0.97, P = 0.024; aOR 0.29, 95%CI 0.08–0.84, P = 0.021). For iCCA severe complications (aOR 0.65 95%CI 0.43–0.99 , P = 0.043) also decreased. No significant outcome differences were observed in pCCA. The number of centres performing liver resections decreased from 26 to 22 between 2014 and 2022, while median annual volumes did not change (40–49, P = 0.66). Over time, postoperative mortality and FTR decreased after liver surgery, despite treating higher-risk patients. The DHBA continues its focus on providing feedback and benchmark results to further enhance outcomes. [ABSTRACT FROM AUTHOR]

Intraoperative radiofrequency ablation (RFA) and the newer technique of microwave ablation (MWA) can both be of additional value in parenchyma preserving surgical treatment of colorectal liver metastases (CRLM). MWA is less influenced by the heat-sink effect of surrounding vessels and can generate more heat in less time but RFA is still widely used. True comparing studies are scarce. This single centre retrospective cohort study analyzed patients who underwent ultrasound guided intraoperative ablation as a part of the surgical treatment of CRLM between 2013 and 2018. In September 2015, MWA was substituted for RFA. Outcomes included unsuccessful ablation rates at 1-year postoperative, 30-days major complication rates, progression free survival (PFS) and overall survival (OS). Logistic regression models were used for univariable and multivariable analyses to identify predictors of unsuccessful ablation. Forty-one patients underwent RFA of 98 lesions (median 2) and 79 patients underwent MWA of 193 lesions (median 2). The median diameter of the ablated lesions was 9 mm for both RFA and MWA. Unsuccessful ablation was observed in 7 metastases (7.1%) after RFA and 14 metastases (7.3%) after MWA (p = 1.000). Complications requiring re-intervention were observed after 8 procedures, 2 complications in the RFA group (4.9%) versus 6 complications in the MWA group (7.6%, p = 0.714), of which 6 were liver-related. Ninety-day mortality did not occur. Ablation technique was not associated with unsuccessful ablations. CRLM size was associated with unsuccessful ablation in the per lesion analysis (p < 0.001). Intraoperative RFA and MWA were equally effective for treatment of small CRLM. [ABSTRACT FROM AUTHOR]

Right-sided and left-sided colorectal cancer (CRC) is known to differ in their molecular carcinogenic pathways. The prevalence of sarcopenia is known to worsen the outcome after hepatic resection. We sought to investigate the prevalence of sarcopenia and its prognostic application according to the primary CRC tumor site. 355 patients (62% male) who underwent liver resection in our center were identified. Clinicopathologic characteristics and long-term outcomes were stratified by sarcopenia and primary tumor location (right-sided vs. left-sided). Tumors in the coecum, right sided and transverse colon were defined as right-sided, tumors in the left colon and rectum were defined as left-sided. Sarcopenia was assessed using the skeletal muscle index (SMI) with a measurement of the skeletal muscle area at the level L3. Patients who underwent right sided colectomy (n = 233, 65%) showed a higher prevalence of sarcopenia (35.2% vs. 23.9%, p = 0.03). These patients also had higher chances for postoperative complications with Clavien Dindo >3 (OR 1.21 CI95% 0.9–1.81, p = 0.05) and higher odds for mortality related to CRC (HR 1.2 CI95% 0.8–1.8, p = 0.03).On multivariable analysis prevalence of sarcopenia remained independently associated with worse overall survival and disease free survival (overall survival: HR 1.47 CI 95% 1.03–2.46, p = 0.03; HR 1.74 CI95% 1.09–3.4, p = 0.05 respectively). Sarcopenia is known to have a worse prognosis in patients with CRLM and CRC. Depending on the primary location sarcopenia has a variable effect on the outcome after liver resection. [ABSTRACT FROM AUTHOR]

Widespread differences in patient demographics and disease burden between hospitals for resection of colorectal liver metastases (CRLM) have been described. In the Netherlands, networks consisting of at least one tertiary referral centre and several regional hospitals have been established to optimize treatment and outcomes. The aim of this study was to assess variation in case-mix, and outcomes between these networks. This was a population-based study including all patients who underwent CRLM resection in the Netherlands between 2014 and 2019. Variation in case-mix and outcomes between seven networks covering the whole country was evaluated. Differences in case-mix, expected 30-day major morbidity (Clavien-Dindo ≥3a) and 30-day mortality between networks were assessed. In total 5383 patients were included. Thirty-day major morbidity was 5.7% and 30-day mortality was 1.5%. Significant differences between networks were observed for Charlson Comorbidity Index, ASA 3+, previous liver resection, liver disease, preoperative MRI, preoperative chemotherapy, ≥3 CRLM, diameter of largest CRLM ≥55 mm, major resection, combined resection and ablation, rectal primary tumour, bilobar and extrahepatic disease. Uncorrected 30-day major morbidity ranged between 3.3% and 13.1% for hospitals, 30-day mortality ranged between 0.0% and 4.5%. Uncorrected 30-day major morbidity ranged between 4.4% and 6.0% for networks, 30-day mortality ranged between 0.0% and 2.5%. No negative outliers were observed after case-mix correction. Variation in case-mix and outcomes are considerably smaller on a network level as compared to a hospital level. Therefore, auditing is more meaningful at a network level and collaboration of hospitals within networks should be pursued. [ABSTRACT FROM AUTHOR]

Nearly half of patients with colorectal cancer develop liver metastases. Radical resection of colorectal liver metastases (CRLM) offers the best chance of cure, significantly improving 5-year survival. Recurrence of metastatic disease is common, occurring in 60 % or more of patients. Clinical equipoise exists regarding the role of perioperative chemotherapy in patients with resected CRLM. This investigation sought to clarify the efficacy of perioperative chemotherapy in patients that have undergone curative-intent resection of CRLM. A systematic review and meta-analysis was completed of randomized controlled trials (RCTs) comparing perioperative chemotherapy to surgery alone in patients with resected CRLM. MEDLINE (Ovid), EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched, as well as abstracts from recent oncology conferences. A meta-analysis was performed pooling the hazard ratios for disease-free survival (DFS) and overall survival (OS), using a random-effects model. A total of five, phase 3, open-label, RCTs were included resulting in a pooled analysis of 1119 of the total 1146 enrolled patients. 559 patients were randomized to perioperative chemotherapy and 560 to surgery alone. Pooled estimates demonstrated a statistically significant improvement in DFS (HR 0.71, 95 % CI: 0.61–0.82; p < 0.001) but not OS (HR 0.87, 95 % CI: 0.73–1.04; p = 0.136). Perioperative chemotherapy in the setting of resected CRLM resulted in an improvement in DFS, however this did not translate into an OS benefit. Poor compliance to post-hepatectomy oxaliplatin-based chemotherapy regimens was identified. Further investigation into the optimal regimen and sequencing of perioperative chemotherapy is justified. [ABSTRACT FROM AUTHOR]

how best to manage patients with colorectal cancer and synchronous liver metastasis is still controversial, with specific concerns of increased risk of postoperative complications following combined resection. We aimed at analyzing the influence of combined liver resection on the risk of anastomotic leak (AL) following colorectal resection. we reviewed the iCral prospectively maintained database to compare the relative risk of AL of patients undergoing colorectal resection for cancer to that of patients receiving simultaneous liver and colorectal resection for cancer with isolated hepatic metastases. The incidence of AL was the primary outcome of the analysis. Perioperative details and postoperative complications were also appraised. out of a total of 996 patients who underwent colorectal resection for cancer, 206 receiving isolated colorectal resection were compared with a matched group of 53 patients undergoing simultaneous liver and colorectal resection. Combined surgery had greater operative time and resulted in longer postoperative hospitalization compared to colorectal resection alone. The proportion of overall morbidity following combined resection was significantly higher than after isolated colorectal resection (56.6% vs. 37.9%, p = 0.021). Overall, the two groups of patients did not differ neither on the rate of major postoperative complications, nor in terms of AL (9.4% vs. 6.3%, p = 0.381). At specific multivariate analysis, the duration of surgery was the only risk factor independently associated with the likelihood of AL. combining hepatic with colorectal resection for the treatment of synchronous liver metastasis from colorectal cancer does not increase significantly the incidence of AL. • Over the last decade there has been a growing interest in performing simultaneous resection of colorectal cancer with synchronous metastases confined to the liver. • Despite some concerns have been raised regarding a higher risk of postoperative morbidity, clinical evidence focusing on specific surgical-related morbidity is still scarce. • This study aims at comparing the relative risk of anastomotic failure in patients receiving isolated colorectal resection vs. patients undergoing colorectal resection in combination with liver metastasis resection. • By comparing well-matched groups of patients, this analysis demonstrates that simultaneous colorectal and liver resection does not confer a significantly higher risk of anastomotic leakage as compared to colorectal resection alone. [ABSTRACT FROM AUTHOR]

Data regarding clinical outcomes of patients undergoing hepatic resection for BRAF -mutated colorectal liver metastases (CRLM) are scarce. Most of the studies report an impaired median overall survival (OS) in BRAF -mutated patients, but controversial Results regarding both recurrence-free survival (RFS) and recurrence patterns. The purpose of this updated meta-analysis was to better precise the impact of BRAF mutations on clinical outcomes following liver surgery for CRLM study, especially on recurrence. A systematic literature review was performed to identify articles reporting clinical outcomes including both OS and RFS, recurrence patterns, and clinicopathological details of patients who underwent complete liver resection for CRLM, stratified according to BRAF mutational status. Thirteen retrospective studies, including 5192 patients, met the inclusion criteria. The analysis revealed that both OS (OR = 1.981; 95% CI = [1.613–2.432]) and RFS (OR = 1.49; 95% CI [1.01–2.21]) were impaired following liver surgery for CRLM in BRAF -mutated patients. Risks of both hepatic (OR = 0.42; 95% CI [0.18–0.98]) and extrahepatic recurrences (OR = 0.53; 95% CI [0.33–0.83] were significantly higher in BRAF -mutated patients. These patients tended to have higher rates of right-sided colon primary tumors, primary positive lymph nodes, and multiple CRLM. This meta-analysis confirms that BRAF mutations impair both OS and RFS following liver surgery. Therefore, BRAF mutational status should probably be included in further prognostic scores for the assessment of the expected clinical outcomes following surgery for CRLM. [ABSTRACT FROM AUTHOR]

The clinical role of lymphadenectomy (LAD) as part of hepatic resection for malignancies of the liver remains unclear. In this study, we aimed to report on the use cases and postoperative outcomes of liver resection and simultaneous LAD for hepatic malignancies (HM). Clinicopathological data from patients who underwent surgery at 13 German centers from 2017 to 2022 (n = 3456) was extracted from the StuDoQ|Liver registry of the German Society of General and Visceral Surgery. Propensity-score matching (PSM) was performed to account for the extent of liver resection and patient demographics. LAD was performed in 545 (16%) cases. The most common indication for LAD was cholangiocarcinoma (CCA), followed by colorectal liver metastases (CRLM) and hepatocellular carcinoma (HCC). N+ status was found in 7 (8%), 59 (35%), and 56 cases (35%) for HCC, CCA, and CRLM, respectively (p < 0.001). The LAD rate was highest for robotic-assisted resections (28%) followed by open (26%) and laparoscopic resections (13%), whereas the number of resected lymph nodes was equivalent between the techniques (p = 0.303). LAD was associated with an increased risk of liver-specific postoperative complications, especially for patients with HCC. In this multicenter registry study, LAD was found to be associated with an increased risk of liver-specific complications. The highest rate of LAD was observed among robotic liver resections. [ABSTRACT FROM AUTHOR]

Textbook outcome (TO) represents a multidimensional quality measurement, encompassing the desirable short-term outcomes following surgery. This study aimed to investigate whether achieving TO after resection of colorectal liver metastases (CRLM) surgery is related to better overall survival (OS) in a national cohort. Data was retrieved from the Dutch Hepato Biliary Audit. A modified definition of TO (mTO) was used because readmissions were only recorded from 2019. mTO was achieved when no severe postoperative complications, mortality, prolonged length of hospital stay, occurred and when adequate surgical resection margins were obtained. To compare outcomes of patients with and without mTO and reduce baseline differences between both groups propensity score matching (PSM) was used for patients operated on between 2014 and 2018. Out of 6525 eligible patients, 81 % achieved mTO. For the cohort between 2014 and 2018, those achieving mTO had a 5-year OS of 46.7 % (CI 44.8–48.6) while non-mTO patients had a 5-year OS of 33.7 % (CI 29.8–38.2), p < 0.001. Not achieving mTO was associated with a worse OS (aHR 1.34 (95 % CI 1.17–1.53), p < 0.001. Median follow-up was 76 months., PSM assigned 519 patients to each group. In the PSM cohort patients achieving mTO, 5-year OS was 43.6 % (95 % CI 39.2–48.5) compared to 36.4 % (95 % CI 31.9–41.2) in patients who did not achieve mTO, p = 0.006. Achieving mTO is associated with improved long-term survival. This emphasizes the importance of optimising perioperative care and reducing postoperative complications in surgical treatment of CRLM. [ABSTRACT FROM AUTHOR]

R0 margin is the standard in the surgical treatment of colorectal liver metastases (CLM). Recently R1 surgery, at least that enabling CLM vessel-detachment (R1vasc), seems comparable to R0. As a possible background of that biologic factors could play some role. Among them, KRAS has been investigated in the present study. Patients who underwent curative surgery for CLM between 2008 and 2016 were identified. R0, R1vasc and parenchymal R1 (R1par; tumor exposure once dissected from the parenchyma) resections with known KRAS status were analyzed. Of 1000 resection areas in 340 patients, 654 (65%) R0, 98 (10%) R1vasc and 248 (25%) R1par. In mutated KRAS (mKRAS), local recurrence (LR) was similar between R0 and R1vasc (per-patient 4,8% vs. 2%, p = 0.628; per-area 2,1% vs. 1,9%, p = 0.940), while higher in R1par (per-patient 25,4% and per-area 19,5%; p < 0.001 for both). In wild-type KRAS (wtKRAS), R0 had less LR compared to R1vasc (per-patient 7,6% vs 14,6%, p = 0.335; per-area 3,1% vs 13,3%, p = 0.012) and R1par (per-patient 18,3%, p = 0.060; per-area 9,9%, p = 0.013). KRAS did not impact LR in R0 (per-patient 7,6% vs. 4,8%, p = 0.491; per-area 3,1% vs. 2,1%, p = 0.555), while wtKRAS R1par had less LR compared to mKRAS R1par (per-patient 18,3% vs 25,4%, p = 0.404; per-area 9,9% vs 19,5%, p = 0.048). Inversely, LR was increased in wtKRAS R1vasc compared to mKRAS R1vasc (per-patient 14,6% vs 2%, p = 0.043; per-area 13,3% vs 1,9%, p = 0.046). KRAS status does not impact LR risk in R0 resection. Inversely, R1vasc vs R1par LR risk is reduced in mKRAS, and increased in wtKRAS. If confirmed these results are of note. [ABSTRACT FROM AUTHOR]

Two-stage hepatectomy (TSH) has increased the chance of surgical resections for bilobar colorectal liver metastases (CRLM). Nevertheless, drop-out between stages and early recurrence rates raise the question of surgical futility in some situations. This study aimed to identify factors of TSH oncological failure. Patients with bilobar CRLM eligible for TSH in three tertiary centers between 2010 and 2021 were included, and divided in Failure and Success groups. Oncological failure was defined as failure of the second stage hepatectomy for tumor progression or recurrence within 6 months after resection. Among 95 patients, 18 (18.9%) had hepatic progression between the two stages, and 7 (7.4%) failed to complete the second stage hepatectomy. After TSH, 31 (32.6%) patients experienced early recurrence. Overall, 38 (40.0%) patients experienced oncological failure (Failure group). The Failure group had lower median DFS (3 vs. 32 months, p < 0.001) and median OS (29 vs. 70 months, p = 0.045) than the Success group. On multivariable analysis, progression between the two stages in the future liver remnant (OR = 15.0 (3.22–113.0), p = 0.002), and maximal tumor size ≥40 mm in the future liver remnant (OR = 13.1 (2.12–117.0), p = 0.009) were independent factors of oncological failure. Recurrence between the two stages and maximal tumor size ≥40 mm in the future liver remnant were associated with TSH failure for patients with bilobar CRLM. • 40% of patients who underwent two stage hepatectomy for colorectal liver metastases will experience oncological failure. • Oncological failure significantly shorten disease-free and overall survival. • Recurrence between the two stages and maximal tumor size ≥40 mm in the future liver remnant are associated with two-stage hepatectomy failure. [ABSTRACT FROM AUTHOR]

Recurrence post hepatectomy for colorectal liver metastases (CRLM) occurs in 70 % of patients within two years. No established guidance on the method or intensity of follow-up currently exists. The aim of this systematic review was to summarise literature and determine whether it is possible to identify an optimal follow up regime. To this date there are no randomised prospective studies investigating this. A systematic review was performed according to PRISMA guidelines. Outcomes included general demographics, method, frequency and duration of follow up, survival and recurrence data. Quality assessment of the papers was performed. Twenty-five articles published between 1994 and 2022 were included, including 9945 patients. CT was the most common imaging modality (n = 14) and CEA most common blood test (n = 11). Intensity of follow up was higher in the first two years post resection and only two papers continued follow up post 5 years resection. There was wide variation in outcome measures - Overall survival (OS) was most commonly reported. Nine papers reported OS ranging between 39 and 78.1 %. There is wide variation in follow up methods and outcome reporting. There is no strong evidence to support intensive follow up, and the benefits of long term follow up are also unknown due to the lack of patient centred data. High quality, prospective studies should be the focus of future research as further retrospective data is unlikely to resolve uncertainties around optimal follow up. [ABSTRACT FROM AUTHOR]

The definition of R1 resection in colorectal cancer liver metastases (CRLM) remains debatable. This retrospective study was conducted to clarify the impact of R1 margin on patient survival after liver resection for CRLM, taking into consideration tumor biology, including RAS status and chemotherapy response. We retrospectively analysed the clinical and survival data of 214 CRLM patients with initially resectable liver metastases who underwent liver resection after receiving neoadjuvant chemotherapy between January 2006 and December 2016. R1 resection significantly impacted patients' overall survival (OS) and disease-free survival (DFS) in the overall patient cohort (5-year OS: 53.2% for R0 vs 38.2% for R1, P = 0.001; 5-year DFS: 26.5% for R0 vs 10.5% for R1, P = 0.002). In the RAS wild-type subgroup and respond to chemotherapy (RC) subgroup, R1 reached a similar OS to those who underwent R0 resection (RAS wild-type, P = 0.223; RC, P = 0.088). For the RAS mutated subgroup and no response to chemotherapy (NRC) subgroup, OS was significantly worse underwent R1 resection (RAS mutant, P = 0.002; NRC, P = 0.022). When considering tumor biology combining RAS and chemotherapy response status, R1 resection was only acceptable in patients with both RAS wild-type and RC (5-year OS: 66.4% for R0 vs 65.2% for R1, p = 0.884), but was significantly worse in those with either RAS mutation or NRC. Tumor biology plays an important role in deciding the appropriate resection margin in patients with CRLM undergoing radical surgery. R1 resection margin is only acceptable in RAS wild-type patients who respond to chemotherapy. [ABSTRACT FROM AUTHOR]

Location of the primary tumor side has become an increasingly prognostic factor for colorectal liver metastasis. The present study was to perform a meta-analysis to investigate if primary right-sided tumor impacted on long-term survival outcome of colorectal liver metastases following local treatment. Eligible trials were identified from the Embase, PubMed, Web of Science and the Cochrane database that were published before October in 2018. English language trials that compared long-term survival outcome of primary left-sided tumor with right-sided tumor colorectal liver metastases following local treatment were included. Hepatic resection for colorectal liver metastases was investigated. The main study outcomes included overall survival and disease free survival of primary right-sided colorectal liver metastases following local treatment. The risk factors of largest tumor size, primary node metastases, multiple tumor and RAS mutation were also analyzed. A systematic review and meta-analysis was done using a fixed-effects model. Hazard ratio with a 95% confidence interval was used to measure the pooled effect. A total of twelve studies with 6387 patients were included. For primary right-sided colorectal liver metastases patients following hepatic resection, the overall pooled HR for 5-year overall survival rate was 1.354 (95% CI: 1.238–1.482; p = 0.000; I 2 = 33.7%, p = 0.138). The pooled HR for 5-year disease free survival rate of primary right-sided CRLM in the included studies calculated using the fix-effects model was 1.104 (95% CI: 0.987–1.235; p = 0.084; I 2 = 0%, p = 0.477). It demonstrated that primary right-sided for colorectal liver metastases location was a significantly worse prognostic factor in terms of overall survival. [ABSTRACT FROM AUTHOR]

Multidisciplinary management of metastatic colorectal liver metastases (CRLM) is still challenging. To assess postoperative complications in initially unresectable or borderline resectable CRLM, the prospective EORTC-1409 ESSO 01-CLIMB trial capturing 'real-life data' of European centres specialized in liver surgery was initiated. A total of 219 patients were registered between May 2015 and January 2019 from 15 centres in nine countries. Eligible patients had borderline or initially unresectable CRLM assessed by pre-operative multidisciplinary team discussion (MDT). Primary endpoints were postoperative complications, 30-day and 90-days mortality post-surgery, and quality indicators. We report the final results of the 151 eligible patients that underwent at least one liver surgery. Perioperative chemotherapy with or without targeted treatment were administered in 100 patients (69.4%). One stage resection (OSR) was performed in 119 patients (78.8%). Two stage resections (TSR, incl. Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy (ALPPS)) were completed in 24 out of 32 patients (75%). Postoperative complications were reported in 55.5% (95% CI: 46.1–64.6%), 64.0% (95% CI: 42.5–82%), and 100% (95% CI: 59–100%) of the patients in OSR, TSR and ALPPS, respectively. Post-hepatectomy liver failure occurred in 6.7%, 20.0%, and 28.6% in OSR, TSR, and ALPPS, respectively. In total, four patients (2.6%) died after surgery. Across nine countries, OSR was more often performed than TSR and tended to result in less postoperative complications. Despite many efforts to register patients across Europe, it is still challenging to set up a prospective CRLM database. [ABSTRACT FROM AUTHOR]

A nationwide multicenter study was performed to examine short- and long-term effects of irreversible electroporation (IRE) for hepatocellular carcinoma (HCC) and colorectal cancer liver metastases (CRCLM). IRE is an alternative method when thermal ablation is contraindicated because of risk for serious thermal complications. All consecutive patients in Sweden treated with IRE because of HCC or CRCLM, were included between 2011 and 2018. We evaluated medical records and radiological imaging to obtain information regarding patient-, tumor-, and treatment characteristics. We also assessed local tumor progression, and survival. In total 206 tumors in 149 patients were treated with IRE. Eighty-seven patients (58.4%) had colorectal cancer liver metastases, and 62 patients (41.6%) had hepatocellular carcinoma. Median tumor size was 20 mm (i.q.r. 14–26 mm). Median overall survival for CRCLM and HCC, were 27.0 months (95% CI 22.2–31.8 months), and 35.0 months (95% CI 13.8–56.2 months), respectively. Median follow-up time was 58 months (95% CI 50.6–65.4). Local ablation success at six and twelve months for HCC was 58.3% and 40.3%, and for CRCLM 37.7% and 25.4%. The median time to local tumor progression (LTP) for HCC was 21.0 months (95% CI: 9.5–32.5 months), and for CRCLM 6.0 months (95% CI: 4.5–7.5 months). At 30-day follow-up, 15.4% (n = 23) of patients suffered from a complication rated as Clavien-Dindo grade 1-3a. Three patients (2.0%) had grade 3b-5 with one death in a thromboembolic event. IRE is a safe ablation modality for patients with liver tumors that are located in such a way that other treatment options are unsuitable. • IRE is a safe treatment modality with low morbidity and good efficacy for patients with liver tumors that are located in such a way that other treatment options are unsuitable. • IRE appears to be more effective in treating hepatocellular cancer (HCC) compared to colorectal cancer liver metastases (CRCLM). • For patients with CRCLM, larger tumor size (>10 mm) resulted in earlier local tumor progression. This was not the case for patients with HCC. [ABSTRACT FROM AUTHOR]

Routine treatment with preoperative systemic chemotherapy (CTx) in patients with colorectal liver metastases (CRLM) remains controversial due to lack of consistent evidence demonstrating associated survival benefits. This study aimed to determine the effect of preoperative CTx on overall survival (OS) compared to surgery alone and to assess hospital and oncological network variation in 5-year OS. This was a population-based study of all patients who underwent liver resection for CRLM between 2014 and 2017 in the Netherlands. After 1:1 propensity score matching (PSM), OS was compared between patients treated with and without preoperative CTx. Hospital and oncological network variation in 5-year OS corrected for case-mix factors was calculated using an observed/expected ratio. Of 2820 patients included, 852 (30.2%) and 1968 (69.8%) patients were treated with preoperative CTx and surgery alone, respectively. After PSM, 537 patients remained in each group, median number of CRLM; 3 [IQR 2–4], median size of CRLM; 28 mm [IQR 18–44], synchronous CLRM (71.1%). Median follow-up was 80.8 months. Five-year OS rates after PSM for patients treated with and without preoperative chemotherapy were 40.2% versus 38.3% (log-rank P = 0.734). After stratification for low, medium, and high tumour burden based on the tumour burden score (TBS) OS was similar for preoperative chemotherapy vs. surgery alone (log-rank P = 0.486, P = 0.914, and P = 0.744, respectively). After correction for non-modifiable patient and tumour characteristics, no relevant hospital or oncological network variation in five-year OS was observed. In patients eligible for surgical resection, preoperative chemotherapy does not provide an overall survival benefit compared to surgery alone. [ABSTRACT FROM AUTHOR]

The efficacy of combining ablation and resection (CARe) in treating unresectable colorectal cancer liver metastases (CRLM) was well established. This study aimed to investigate the surgical and oncological outcomes of CARe strategy focusing on initially resectable CRLM. A total of 971 patients with resectable CRLM from a retrospective database of 1414 CRLM patients were enrolled, including 120 in the CARe group and 851 in the hepatectomy alone group. Short- and long-term outcomes were compared between groups using propensity score matching analysis. After propensity score matching, 96 matched pairs of patients from each group were included. General characteristics of primary tumour and liver metastases were not statistically different between the CARe group and hepatectomy alone group. Disease-free survival (p = 0.257), intrahepatic recurrence-free survival (p = 0.329), and overall survival (p = 0.358) were similar between the two groups. Patients in CARe group had significantly reduced rate of major hepatectomy (5.2% vs. 21.9%, p = 0.001), lower incidence of postoperative hepatic insufficiency (0.0% vs. 5.2%, p = 0.023), and shortened postoperative hospital stay (7 d vs. 8 d, p = 0.019). Multivariate analysis showed that surgical approach did not affect oncologic outcome; liver metastasis with diameter >3 cm was an independent prognostic factor for hepatic recurrence-free and disease-free survival, and RAS status and lymph node metastasis at the primary site were independent prognostic factors for overall survival. For patients with resectable CRLM, CARe may be a better treatment strategy than hepatectomy alone, as it could avoid major hepatectomy and get better surgical outcomes, while providing the similar oncologic results. [ABSTRACT FROM AUTHOR]

Postoperative infectious complications (PIC) remain one of the most common complications after surgery. The influence of PIC on long-term survival for patients after liver surgery for colorectal liver metastases (CRLM) needs further investigation. Data of patients who underwent liver resection for CRLM between 2012 and 2017 at the Department of Surgery, Campus Charité Mitte and Campus Virchow-Klinikum, Charité – Universitätsmedizin Berlin were evaluated. Overall survival (OS) was stratified according to the development of PIC. Independent predictors of PIC and diminished survival were identified using regression models. Of 270 patients, eighty-four (31%) patients developed PIC including intraabdominal infections (n = 51, 61%), cholangitis (n = 5, 6%), pneumonia (n = 12, 14%), wound infections (n = 28, 33%), urinary tract infections (n = 5, 6%), or central line-associated bloodstream infections (n = 4, 5%). PIC were associated with a significantly diminished five-year OS (30% vs. 43%, p = 0.008). Age >65 years (p = 0.016, hazard ratio [HR] = 2.2, 95% confidence interval [CI] = 1.2–4.0), comorbidity (p = 0.019, HR [95% CI] = 2.4 [1.2–4.9]), simultaneous resection of primary tumor (p = 0.005, HR [95% CI] = 4.3 [1.6–11.9]), biliary drainage (p < 0.001, HR [95% CI] = 4.1 [2.0–8.5]), and length of procedure ≥272 min (p = 0.012, HR [95% CI] = 2.2 [1.2–4.1]) were independent predictors for the development of PIC. Body-mass index (BMI) > 30 kg/m2 (p = 0.002, HR [95% CI] = 2.4 [1.4–4.0]), postoperative major complications (p = 0.003, HR [95% CI] = 2.2 [1.3–3.8]), and 3- or 4-MRGN bacteria (p = 0.001, HR [95% CI] = 7.7 [2.2–27.3]) were independently associated with diminished OS. PIC are associated with diminished OS after resection for CRLM. Age >65 years, comorbidities, simultaneous resection of the primary tumor, and biliary drainages were identified as independent risk factors for the development of PIC. High BMI, postoperative major morbidity and 3-/4-MRGN bacteria were independently predictive of worse OS. These factors need to be considered in perioperative management for patients with CRLM. [ABSTRACT FROM AUTHOR]

Background Primary tumour location has long been debated as a prognostic factor in colorectal cancer patients with liver metastases (CRLM) undergoing liver resection. This retrospective study was conducted to clarify the prognostic value of tumour location after radical hepatectomy for CRLM and its underlying causes. Methods We retrospectively analysed clinical data from 420 patients with CRLM whom underwent liver resection between January 2002 and December 2015. Right-sided (RS) tumours include tumours located in the cecum, ascending colon, and transverse colon, and left-sided (LS) tumours include those located in the splenic flexure, descending colon, sigmoid colon, and rectum. Results Both overall survival (OS) and disease-free survival (DFS) were similar between patients with RS and LS primary tumours (5-year OS: 46.5% vs 38.3%, P = 0.699; 5-year DFS: 29.1% vs 22.4%, P = 0.536). Specifically, RAS mutation rate was significantly higher in patients with RS tumours (P = 0.007). Subgroup analysis showed that the RAS mutation on the LS and RS tumours have different prognostic impact for CRLM patients on long-term survival after hepatic resection (RS, OS: P = 0.437, DFS: P = 0.471; LS, OS: P < 0.001, DFS: P = 0.002). The multivariable analysis showed that RAS mutant is an independent factor influencing OS in patients with LS primary tumour only. Conclusions The site of the primary tumour has no significant impact on the long-term survival in patients with CRLM undergoing radical surgery. However, prognostic value of RAS status differs depending on the site of the primary tumour. [ABSTRACT FROM AUTHOR]